Atherosclerotic cardiovascular disease risk and small dense low-density lipoprotein cholesterol in men, women, African Americans and non-African Americans: The pooling project

• Published in: Atherosclerosis Vol. 367; pp. 15 - 23
• Main Authors: Schaefer, Ernst J., Ikezaki, Hiroaki, Diffenderfer, Margaret R., Lim, Elise, Liu, Ching-Ti, Hoogeveen, Ron C., Guan, Weihua, Tsai, Michael Y., Ballantyne, Christie M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.02.2023
• Subjects: Atherosclerosis - diagnosis; Atherosclerosis - epidemiology; Atherosclerotic cardiovascular disease; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - epidemiology; Cholesterol; Cholesterol, LDL; Female; Humans; Male; Middle Aged; Pooled cohort equation; Risk Factors; sdLDL cholesterol; Atherosclerotic cardiovascular disease; sdLDL cholesterol; Pooled cohort equation
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2023.01.015

Elevated small dense low-density lipoprotein-cholesterol (sdLDL-C) has been reported to be associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. Our aims were to determine whether direct and calculated sdLDL-C were significant independent ASCVD risk factors in sex and race subgroups. In a total of 15,933 participants free of ASCVD at baseline (median age 62 years, 56.7% female, 19.7% African American) fasting plasma lipids and sdLDL-C were measured by standardized automated methods. All subjects were followed for 10 years for incident ASCVD, which developed in 9.7% of subjects. SdLDL-C values were also calculated. Univariate and multivariate analyses were carried out to assess for independent associations with incident ASCVD after adjustment for all standard risk factors. All standard risk factors were significantly associated with incident ASCVD on univariate analysis, as were direct and calculated sdLDL-C. These latter parameters were also significant when added to the pooled cohort risk equation. However, associations were significantly stronger for direct sdLDL-C and were not significant for calculated values once direct values were in the model. In contrast to calculated values, top quartile direct sdLDL-C was significantly independently associated with incident ASCVD versus bottom quartile values in all subjects and subgroups, except African Americans (hazard ratios ≥1.50, p < 0.01). Subjects with direct values ≥ 50 mg/dL versus <25 mg/dL had significantly higher independent ASCVD risk in all groups (hazard ratios >1.49, all p < 0.01). Having a direct small dense low-density lipoprotein cholesterol value ≥ 50 mg/dL is a significant independent ASCVD risk-enhancer. [Display omitted] •An elevated direct sdLDL-C value > 50 mg/dL is an independent atherosclerotic cardiovascular disease (ASCVD) risk factor.•An elevated calculated sdLDL-C is not an independent ASCVD risk factor.•An elevated direct sdLDL-C value > 50 mg/dL is an ASCVD risk-enhancer.